PALB2 mutations in German and Russian patients with bilateral breast cancer

Bogdanova, Natalia; Sokolenko, Anna P.; Iyevleva, Aglaya G.; Abysheva, Svetlana N.; Blaut, Magda; Bremer, Michael; Christiansen, Hans; Rave-Fränk, Margret; Dörk, Thilo; Imyanitov, Evgeny N.

doi:10.1007/s10549-010-1290-4

Cited by 51 publications

(36 citation statements)

References 32 publications

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“…Efforts have been made to investigate the mutation spectrum of PALB2 in breast cancer patients, and deleterious mutations have been reported in various populations such as the British, 8, 23 Irish and Scot, 23 Finnish, 9, 15 Scottish-Canadian, 10 French-Canadian, 11 Spanish, 12 Chinese, 13 South African, 14 Italian, 16, 19, 22 Polish, 17 Netherlander, 18 French, 23 German, 20, 23 Russian, 20 African-American, 23 European-American, 24 as well as Australian and New Zealander. 21, 41 All the deleterious mutations associated with breast cancer found in PALB2 appeared to be singletons, except a few were recurrent mutations (c.3116delA, c.3113G>A, and c.3549C>G in British, 8 c.751C>T in Chinese, 13 c.509-510delGA in Polish, 17 and c.3113G>A in Australian and New Zealander 21 ), and founder mutations (c.1592delT in Finnish 9, 15 and c.2323C>T in French-Canadian 11 ).…”

Section: Discussionmentioning

confidence: 99%

Novel germline PALB2 truncating mutations in African American breast cancer patients

Zheng¹,

Zhang²,

Niu³

et al. 2011

Cancer

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Background It has been demonstrated that PALB2 acts as a bridging molecule between the BRCA1 and BRCA2 proteins and is responsible for facilitating BRCA2-mediated DNA repair. Truncating mutations in the PALB2 gene have been reported to be enriched in Fanconi anemia and breast cancer patients in various populations. Methods We evaluated the contribution of PALB2 germline mutations in 279 African-American breast cancer patients including 29 patients with a strong family history, 29 patients with a moderate family history, 75 patients with a weak family history, and 146 non-familial or sporadic breast cancer cases. Results After direct sequencing of all the coding exons, exon/intron boundaries, 5′UTR and 3′UTR of PALB2, three (1.08%; 3 in 279) novel monoallelic truncating mutations were identified: c.758dupT (exon4), c.1479delC (exon4) and c.3048delT (exon 10); together with 50 sequence variants, 27 of which are novel. None of the truncating mutations were found in 262 controls from the same population. Conclusions PALB2 mutations are present in both familial and non-familial breast cancer among African-Americans. Rare PALB2 mutations account for a small but substantial proportion of breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

Novel germline PALB2 truncating mutations in African American breast cancer patients

Zheng¹,

Zhang²,

Niu³

et al. 2011

Cancer

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“…PALB2 mutations have been identified in the Australian,17,18 Chinese,19 German,20 Italian,21–23 Dutch,24 North American,25–31 Polish,32 Russian,20 South African,33 and Spanish34 populations. No PALB2 mutations have been observed in the geographically confined population of Iceland 35.…”

Section: Prevalence Of Germline Palb2 Mutationsmentioning

confidence: 99%

PALB2 and breast cancer: ready for clinical translation!

Southey¹,

Teo²,

Winship³

2013

TACG

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For almost two decades, breast cancer clinical genetics has operated in an environment where a heritable cause of breast cancer susceptibility is identified in the vast minority of women seeking advice about their personal and/or family history of breast and/or ovarian cancer. A new wave of genetic information is upon us that promises to provide an explanation for the greater proportion of current missing heritability of breast cancer. Whilst researchers refine bioinformatic and analytic methodology necessary to interpret the new genetic data, attention needs to be paid to defining appropriate and coordinated pathways for the translation of this information so that it can be applied in clinical genetic services for the benefit of the majority of women who currently have no explanation for their breast cancer susceptibility. The search for additional breast cancer susceptibility genes remains a very active area of research. Exhausting the power of linkage studies that identified BRCA1 and BRCA2, the research community moved to candidate gene studies that led to the identification of ATM, BRIP1, CHEK2, and PALB2 as so-called “moderate-risk” breast cancer susceptibility genes. Mutations in these genes are rare and although early reports suggested that, on average, they are associated with moderate risks of breast cancer; population-based studies have demonstrated that at least some mutations in these genes are associated with breast cancer risks that are comparable to the average risk associated with BRCA2 mutations. The search for additional breast cancer susceptibility genes has now moved onto research platforms applying massively parallel sequencing capable of sequencing whole human exomes and genomes in single instrument runs. These programs are identifying a large number of additional putative breast cancer susceptibility genes, many of which are currently undergoing validation. It is highly anticipated that the remaining missing heritability of breast cancer will be due to mutations in many different genes, each explaining a small proportion of the currently unexplained heritable breast cancer susceptibility. The characterization of PALB2 as a breast cancer susceptibility gene and subsequent research that has refined our understanding of the prevalence and penetrance of heritable mutations in PALB2 offers a precious opportunity to use the data as a model and develop modes of translation that would be appropriate for the anticipated volume of imminent new information.

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“…Mutations in PALB2 are rare (varying from 0.1% to 1.5% depending upon the population) (Foulkes et al , 2007; Rahman et al , 2007; Tischkowitz et al , 2007; Dansonka-Mieszkowska et al , 2010; Papi et al , 2010; Southey et al , 2010; Bogdanova et al , 2011; Casadei et al , 2011; Ding et al , 2011; Hellebrand et al , 2011; Teo et al , 2013a, 2013b) but for women carrying them, and their relatives who might also be mutation carriers, knowing their mutation status has the potential to be clinically important as carriers are at high risk of breast cancer. Identified mutation carriers could be informed of optimal, risk appropriate clinical screening and treatment.…”

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confidence: 99%

Tumour morphology predicts PALB2 germline mutation status

et al. 2013

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Background:Population-based studies of breast cancer have estimated that at least some PALB2 mutations are associated with high breast cancer risk. For women carrying PALB2 mutations, knowing their carrier status could be useful in directing them towards effective cancer risk management and therapeutic strategies. We sought to determine whether morphological features of breast tumours can predict PALB2 germline mutation status.Methods:Systematic pathology review was conducted on breast tumours from 28 female carriers of PALB2 mutations (non-carriers of other known high-risk mutations, recruited through various resources with varying ascertainment) and on breast tumours from a population-based sample of 828 Australian women diagnosed before the age of 60 years (which included 40 BRCA1 and 18 BRCA2 mutation carriers). Tumour morphological features of the 28 PALB2 mutation carriers were compared with those of 770 women without high-risk mutations.Results:Tumours arising in PALB2 mutation carriers were associated with minimal sclerosis (odds ratio (OR)=19.7; 95% confidence interval (CI)=6.0–64.6; P=5 × 10−7). Minimal sclerosis was also a feature that distinguished PALB2 mutation carriers from BRCA1 (P=0.05) and BRCA2 (P=0.04) mutation carriers.Conclusion:This study identified minimal sclerosis to be a predictor of germline PALB2 mutation status. Morphological review can therefore facilitate the identification of women most likely to carry mutations in PALB2.

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PALB2 mutations in German and Russian patients with bilateral breast cancer

Cited by 51 publications

References 32 publications

Novel germline PALB2 truncating mutations in African American breast cancer patients

Novel germline PALB2 truncating mutations in African American breast cancer patients

PALB2 and breast cancer: ready for clinical translation!

Tumour morphology predicts PALB2 germline mutation status

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